The long-term goal of this project is to understand how physical signals complement chemical signals for modulating cellular functions and interactions with the environment. Adherent cells generate mechanical forces to propel migration and drive environment remodeling. They also use mechanical forces to probe the environment, sense their own physical state, communicate with neighboring cells, and possibly coordinate functions within the cell. Previous studies suggested that these physical interactions regulate cell growth, differentiation, and migration, and affect a broad range of health-related issues such as tissue repair and cancer. This project will apply a combination of materials, microfabrication, micromanipulation, microfluidic, and computational approaches to understand mechanical activities and their regulation at the front and rear of a migrating cell. The first aimis designed to determine how the front end of a cell detects surface rigidity and how cellular mechanical output is regulated in relation to the state of migration. The second aim is designed to determine how the rear end of a cell is positioned, and how microtubules, centrosomes, and intracellular tension may regulate the process. Information from this project will have a broad impact on human health, particularly tissue regeneration, embryogenesis, and cancer treatment.